scholarly journals Validation of a Metabolite Panel for a More Accurate Estimation of Glomerular Filtration Rate Using Quantitative LC-MS/MS

2019 ◽  
Vol 65 (3) ◽  
pp. 406-418 ◽  
Author(s):  
Tiffany A Freed ◽  
Josef Coresh ◽  
Lesley A Inker ◽  
Douglas R Toal ◽  
Regis Perichon ◽  
...  

Abstract BACKGROUND Clinical practice guidelines recommend estimation of glomerular filtration rate (eGFR) using validated equations based on serum creatinine (eGFRcr), cystatin C (eGFRcys), or both (eGFRcr-cys). However, when compared with the measured GFR (mGFR), only eGFRcr-cys meets recommended performance standards. Our goal was to develop a more accurate eGFR method using a panel of metabolites without creatinine, cystatin C, or demographic variables. METHODS An ultra-performance liquid chromatography–tandem mass spectrometry assay for acetylthreonine, phenylacetylglutamine, pseudouridine, and tryptophan was developed, and a 20-day, multiinstrument analytical validation was conducted. The assay was tested in 2424 participants with mGFR data from 4 independent research studies. A new GFR equation (eGFRmet) was developed in a random subset (n = 1615) and evaluated in the remaining participants (n = 809). Performance was assessed as the frequency of large errors [estimates that differed from mGFR by at least 30% (1 − P30); goal <10%]. RESULTS The assay had a mean imprecision (≤10% intraassay, ≤6.9% interassay), linearity over the quantitative range (r2 > 0.98), and analyte recovery (98.5%–113%). There was no carryover, no interferences observed, and analyte stability was established. In addition, 1 − P30 in the validation set for eGFRmet (10.0%) was more accurate than eGFRcr (13.1%) and eGFRcys (12.0%) but not eGFRcr-cys (8.7%). Combining metabolites, creatinine, cystatin C, and demographics led to the most accurate equation (7.0%). Neither equation had substantial variation among population subgroups. CONCLUSIONS The new eGFRmet equation could serve as a confirmatory test for GFR estimation.

2014 ◽  
Vol 29 (6) ◽  
pp. 1195-1203 ◽  
Author(s):  
Li Fan ◽  
Lesley A. Inker ◽  
Jerome Rossert ◽  
Marc Froissart ◽  
Peter Rossing ◽  
...  

2021 ◽  
Author(s):  
Makoto Fukuda ◽  
Naoki Sawa ◽  
Hiroki Mizuno ◽  
Daisuke Ikuma ◽  
Rikako Hiramatsu ◽  
...  

Abstract BackgroundMethotrexate is widely used to treat rheumatoid arthritis (RA) but can cause very serious side effects, including pancytopenia, in patients with renal impairment who have an estimated glomerular filtration rate (GFR) of <60 ml/min/1.73m2. In patients with low muscle volume such as elderly patients, GFR can be measured as higher value when calculated using serum creatinine [eGFR(cre)], so more accurate estimation using cystatin C [eGFR(cys)] is preferred.MethodWe evaluated 173 patients with RA who visited Toranomon Hospital in 2019 for factors that may contribute to the difference between eGFR(cre) and eGFR(cys) [eGFR(cre−cys)]. Activities of daily living (ADL) (walking, 1 point; using a cane, 2 points; using a wheelchair, 3 points) was added as a parameter.ResultsIn univariate analysis using Spearman's rank correlation coefficient, eGFR(cre−cys) was negatively correlated with body weight, height, body surface area (BSA), subcutaneous fat area (SFA)/BSA, albumin, and creatinine kinase, and positively correlated with age, erythrocyte sedimentation rate (ESR), and urinary protein. eGFR(cre−cys) was higher in patients who used a cane or wheelchair than those who could walk unaided. Multiple regression analysis showed that ADL and age contribute significantly to eGFR(cre−cys). ConclusionPatients using a cane or wheelchair are susceptible to the higher eGFR(cre−cys) values and overestimation of eGFR(cre), resulting in failed detect subclinical renal dysfunction. For such patients, eGFR(cys) should be evaluated to prevent serious side effects of methotrexate that are easily developed on patients with renal dysfunction.


2020 ◽  
pp. 44-48
Author(s):  
V. A. Aleksandrov ◽  
L. N. Shilova ◽  
A. V. Aleksandrov

The development of renal dysfunction in patients with rheumatoid arthritis (RA) is due to the presence and severity of autoimmune disorders, chronic systemic inflammation, a multiplicity of comorbid conditions, and pharmacotherapy features. The most important parameter that describes the general condition of the kidneys is glomerular filtration rate (GFR). This review presents the data on the possibilities of modern methods for determining estimated GFR (e-GFR) and the specificity of their use in various clinical situations that accompany the course of RA. For the initial assessment of GFR in patients with RA it is advisable to use the measurement of e-GFR based on serum creatinine concentration using the CKD-EPI equation (2009) (with or without indexing by body surface area). In cases where the e-GFR equations are not reliable enough or the results of this test are insufficient for clinical decision making, the serum cystatin C level should be measured and the combined GFR calculation based on creatinine and cystatin C should be used.


Renal Failure ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 1104-1114
Author(s):  
Yanan Liu ◽  
Peng Xia ◽  
Wei Cao ◽  
Zhengyin Liu ◽  
Jie Ma ◽  
...  

Author(s):  
Julie Mouron-Hryciuk ◽  
François Cachat ◽  
Paloma Parvex ◽  
Thomas Perneger ◽  
Hassib Chehade

AbstractGlomerular filtration rate (GFR) is difficult to measure, and estimating formulas are notorious for lacking precision. This study aims to assess if the inclusion of additional biomarkers improves the performance of eGFR formulas. A hundred and sixteen children with renal diseases were enrolled. Data for age, weight, height, inulin clearance (iGFR), serum creatinine, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), parathyroid hormone (PTH), albumin, and brain natriuretic peptide (BNP) were collected. These variables were added to the revised and combined (serum creatinine and cystatin C) Schwartz formulas, and the quadratic and combined quadratic formulas. We calculated the adjusted r-square (r2) in relation to iGFR and tested the improvement in variance explained by means of the likelihood ratio test. The combined Schwartz and the combined quadratic formulas yielded best results with an r2 of 0.676 and 0.730, respectively. The addition of BNP and PTH to the combined Schwartz and quadratic formulas improved the variance slightly. NGAL and albumin failed to improve the prediction of GFR further. These study results also confirm that the addition of cystatin C improves the performance of estimating GFR formulas, in particular the Schwartz formula.Conclusion: The addition of serum NGAL, BNP, PTH, and albumin to the combined Schwartz and quadratic formulas for estimating GFR did not improve GFR prediction in our population. What is Known:• Estimating glomerular filtration rate (GFR) formulas include serum creatinine and/or cystatin C but lack precision when compared to measured GFR.• The serum concentrations of some biological parameters such as neutrophil gelatinase-associated lipocalin (NGAL), parathyroid hormone (PTH), albumin, and brain natriuretic peptide (BNP) vary with the level of renal function. What is New:• The addition of BNP and PTH to the combined quadratic formula improved its performance only slightly. NGAL and albumin failed to improve the prediction of GFR further.


2017 ◽  
Vol 50 (6) ◽  
pp. 301-308 ◽  
Author(s):  
Elizabeth LM Barr ◽  
Louise J Maple-Brown ◽  
Federica Barzi ◽  
Jaquelyne T Hughes ◽  
George Jerums ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document